Regulation of c-myb expression in human neuroblastoma cells during retinoic acid-induced differentiation.

We detected expression of the c-myb proto-oncogene, which was initially thought to be expressed in a tissue-specific manner in cells of hematopoietic lineage, in human tissues of neuronal origin. Since the level of c-myb expression declined during fetal development, we studied the regulation of its expression in human neuroblastoma cell lines induced to differentiate by retinoic acid. The expression of c-myb declined during the maturation of neuroblastoma cells, and this change was mediated by a decrease in c-myb transcription.

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Analysis of Asymmetric Cell Division Using Human Neuroblastoma Cell Lines as a Model System

Symmetry ◽

10.3390/sym13101907 ◽

2021 ◽

Vol 13 (10) ◽

pp. 1907

Author(s):

Hideki Izumi ◽

Yasuhiko Kaneko ◽

Akira Nakagawara

Keyword(s):

Cell Division ◽

Cell Lines ◽

Asymmetric Cell Division ◽

Neuroblastoma Cell ◽

Neuroblastoma Cells ◽

Model System ◽

Human Neuroblastoma Cell ◽

Human Neuroblastoma Cells ◽

Human Neuroblastoma ◽

Neuroblastoma Cell Lines

Neuroblastoma is one of the most common childhood solid tumors and develops from neural stem cells that normally comprise the embryonic structure termed the neural crest. Human neuroblastoma cell lines have special properties as they exhibit cell growth and are induced to become mature neurons by drugs such as retinoid. Therefore, we examined asymmetric cell division (ACD) using human neuroblastoma cells as an ACD model, and confirmed that ACD in human cancer cells is evolutionally conserved. Furthermore, we demonstrated that MYCN is involved in cell division fate. We introduce the brief history of ACD study using neuroblastoma cell lines and discuss why human neuroblastoma cells are an ideal model system for clarifying the mechanism of ACD.

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Retinoic acid- and staurosporine-induced bidirectional differentiation of human neuroblastoma cell lines

Experimental Cell Research ◽

10.1016/0014-4827(92)90399-s ◽

1992 ◽

Vol 202 (1) ◽

pp. 17-27 ◽

Cited By ~ 11

Author(s):

R. Slack ◽

B. Lach ◽

A. Gregor ◽

H. Al-Mazidi ◽

P. Proulx

Keyword(s):

Retinoic Acid ◽

Cell Lines ◽

Neuroblastoma Cell ◽

Human Neuroblastoma Cell ◽

Human Neuroblastoma ◽

Neuroblastoma Cell Lines

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Expression of a drug resistance gene in human neuroblastoma cell lines: modulation by retinoic acid-induced differentiation

Molecular and Cellular Biology ◽

10.1128/mcb.9.10.4337-4344.1989 ◽

1989 ◽

Vol 9 (10) ◽

pp. 4337-4344

Author(s):

S E Bates ◽

L A Mickley ◽

Y N Chen ◽

N Richert ◽

J Rudick ◽

...

Keyword(s):

Retinoic Acid ◽

Multidrug Resistance ◽

Resistance Gene ◽

Cell Lines ◽

Neuroblastoma Cell ◽

Drug Accumulation ◽

Human Neuroblastoma Cell ◽

Human Neuroblastoma ◽

Before And After ◽

Neuroblastoma Cell Lines

Expression of a multidrug resistance gene (mdr1) and its protein product, P-glycoprotein (Pgp), has been correlated with the onset of multidrug resistance in vitro in human cell lines selected for resistance to chemotherapeutic agents derived from natural products. Expression of this gene has also been observed in normal tissues and human tumors, including neuroblastoma. We therefore examined total RNA prepared from human neuroblastoma cell lines before and after differentiation with retinoic acid or sodium butyrate. An increase in the level of mdr1 mRNA was observed after retinoic acid treatment of four neuroblastoma cell lines, including the SK-N-SH cell line. Western blot (immunoblot) analysis demonstrated concomitant increases in Pgp. However, studies of 3H-vinblastine uptake failed to show a concomitant Pgp-mediated decrease in cytotoxic drug accumulation. To provide evidence that Pgp was localized on the cell surface, an immunotoxin conjugate directed against Pgp was added to cells before and after treatment with retinoic acid. Incorporation of [3H]leucine was decreased by the immunotoxin in the retinoic acid-treated cells compared with the undifferentiated cells. These results demonstrate that whereas expression of the mdr1 gene can be modulated by differentiating agents, increased levels of expression are not necessarily associated with increased cytotoxic drug accumulation.

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Up-regulation of the integrin alpha 1/beta 1 in human neuroblastoma cells differentiated by retinoic acid: correlation with increased neurite outgrowth response to laminin.

Cell Regulation ◽

10.1091/mbc.2.12.1021 ◽

1991 ◽

Vol 2 (12) ◽

pp. 1021-1033 ◽

Cited By ~ 67

Author(s):

P Rossino ◽

P Defilippi ◽

L Silengo ◽

G Tarone

Keyword(s):

Retinoic Acid ◽

Neuroblastoma Cell ◽

Neuroblastoma Cells ◽

Morphological Differentiation ◽

Laminin Receptor ◽

Human Neuroblastoma Cell ◽

Type I ◽

Human Neuroblastoma ◽

Beta 1 Integrin

Retinoic acid (RA) is known to induce differentiation of neuroblastoma cells in vitro. Here we show that treatment of two human neuroblastoma cell lines, SY5Y and IMR32, with RA resulted in a fivefold increase of the integrin alpha 1/beta 1 expression. The effect was selective because expression of the alpha 3/beta 1 integrin, also present in these cells, was not increased. The up-regulation of the alpha 1/beta 1 differentiated SY5Y cells correlated with increased neurite response to laminin. In fact, RA-treated SY5Y cells elongated neurites on laminin-coated substratum more efficiently compared with untreated cells or cells treated with nerve growth factor, insulin, or phorbol 12-myristate 13-acetate. These three agents induced partial morphological differentiation but did not increase alpha 1 integrin expression. Neurite extension in RA-treated cells was more efficient on laminin than on fibronectin or collagen type I and was inhibited with beta 1 integrin antibodies on all three substrates. Affinity chromatography experiments showed that alpha 1/beta 1 is the major laminin receptor in both untreated and RA-treated SY5Y cells. These data show that RA, a naturally occurring morphogen implicated in embryonic development, can selectively regulate the expression of integrin complexes in neuronal cells and suggest an important role of the alpha 1/beta 1 laminin receptor in the morphological differentiation of nerve cells.

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Amplified N-myc in human neuroblastoma cells is often arranged as clustered tandem repeats of differently recombined DNA.

Molecular and Cellular Biology ◽

10.1128/mcb.9.11.4903 ◽

1989 ◽

Vol 9 (11) ◽

pp. 4903-4913 ◽

Cited By ~ 72

Author(s):

L C Amler ◽

M Schwab

Keyword(s):

Tandem Repeats ◽

Neuroblastoma Cell ◽

Neuroblastoma Cells ◽

Selective Advantage ◽

Central Position ◽

Coding Region ◽

Human Neuroblastoma Cells ◽

Human Neuroblastoma ◽

Low Degrees ◽

Neuroblastoma Cell Lines

Human neuroblastoma cells often carry amplified DNA encompassing the gene N-myc. Amplified N-myc has been found localized in "double minutes" in direct tumor cell preparations. In contrast, later passages carried amplified N-myc almost exclusively within a single homogeneously staining chromosomal region located at a chromosomal site different from the normal location of N-myc. We used pulsed field gel electrophoresis to define the structural arrangement of the amplified DNA. Long-range mapping was facilitated by the presence of several sites for rare cutting restriction endonucleases in the 5' region of N-myc. Amplified DNAs of different neuroblastoma cell lines were heterogeneous in size and had undergone recombination at various distances from N-myc. N-myc occupied a central position within the amplified DNA, and in no case was the coding region affected by recombination. Among neuroblastoma cells, varying proportions of amplified DNA (in some instances close to 100%) consisted of multiple tandem arrays of DNA segments ranging in size from 100 to 700 kilobase pairs. Tumor cells with low degrees of amplification revealed regions of amplified DNA in excess of 1,500 kilobase pairs without apparent rearrangement. Our observations, in concert with the cytogenetic findings, suggest a model of gene amplification which involves unscheduled DNA replication, recombination, and formation of extrachromosomal DNA followed by integration into a chromosome and subsequent in situ multiplication. The central position which N-myc occupies within the amplified sequences and the lack of recombination within the coding region of N-mc indicate that N-myc rather than other genetic information provides the selective advantage for retention of the amplified DNA.

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